The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome: a potential therapeutic target for inflammatory disorders

Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system eli...

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Published inClinical & translational immunology Vol. 10; no. 2; pp. e1247 - n/a
Main Authors Chong, Wai Chin, Shastri, Madhur D, Peterson, Gregory M, Patel, Rahul P, Pathinayake, Prabuddha S, Dua, Kamal, Hansbro, Nicole G, Hsu, Alan C, Wark, Peter A, Shukla, Shakti Dhar, Johansen, Matt D, Schroder, Kate, Hansbro, Philip M
Format Journal Article
LanguageEnglish
Published Australia John Wiley & Sons, Inc 2021
John Wiley and Sons Inc
Wiley
Subjects
Allergens
Alzheimer's disease
Arteriosclerosis
Asthma
Atherosclerosis
Binding sites
Biosynthesis
Chronic obstructive pulmonary disease
Diabetes
Endoplasmic reticulum
endoplasmic reticulum stress
Homeostasis
Immune system
Infections
inflammasome
Inflammasomes
Inflammation
Inflammatory bowel disease
Inflammatory bowel diseases
Inflammatory diseases
inflammatory disorder
Intestine
Kinases
Lung diseases
Metabolism
NLRP3
Obstructive lung disease
Pathogenesis
Pathogens
Physiology
Protein folding
Protein synthesis
Quality control
Review
Rheumatoid arthritis
Sarcoidosis
Therapeutic targets
Transcription factors
NLRP3
inflammatory disorder
inflammasome
endoplasmic reticulum stress
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Abstract Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome‐induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress‐ and inflammasome‐related inflammatory disorders. In this Review, we discuss the state‐of‐the‐art understanding of the pathways and factors involved in ER stress and inflammasome activation. We describe how these pathways induce inflammatory responses and are involved in chronic inflammatory diseases. We discuss new links between ER stress inflammasome activity and inflammation, and potential new therapeutic approaches to suppress ER stress and inflammasome‐induced inflammation.
AbstractList Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome‐induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress‐ and inflammasome‐related inflammatory disorders. In this Review, we discuss the state‐of‐the‐art understanding of the pathways and factors involved in ER stress and inflammasome activation. We describe how these pathways induce inflammatory responses and are involved in chronic inflammatory diseases. We discuss new links between ER stress inflammasome activity and inflammation, and potential new therapeutic approaches to suppress ER stress and inflammasome‐induced inflammation.
Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome‐induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress‐ and inflammasome‐related inflammatory disorders.
Abstract Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome‐induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress‐ and inflammasome‐related inflammatory disorders.
Author Hansbro, Philip M
Hansbro, Nicole G
Patel, Rahul P
Hsu, Alan C
Dua, Kamal
Peterson, Gregory M
Shastri, Madhur D
Pathinayake, Prabuddha S
Chong, Wai Chin
Wark, Peter A
Johansen, Matt D
Schroder, Kate
Shukla, Shakti Dhar
AuthorAffiliation 3 School of Pharmacy and Pharmacology University of Tasmania Hobart TAS Australia
5 Discipline of Pharmacy Graduate School of Health University of Technology Sydney Ultimo NSW Australia
7 Institute for Molecular Bioscience University of Queensland St Lucia QLD Australia
2 Centre for Cancer Research Hudson Institute of Medical Research Clayton VIC Australia
4 Priority Research Centre for Healthy Lungs Hunter Medical Research Institute The University of Newcastle Callaghan NSW Australia
1 Department of Molecular and Translational Science Monash University Clayton VIC Australia
6 Centre for Inflammation Centenary Institute Faculty of Science School of Life Sciences University of Technology Sydney NSW Australia
AuthorAffiliation_xml – name: 4 Priority Research Centre for Healthy Lungs Hunter Medical Research Institute The University of Newcastle Callaghan NSW Australia
– name: 3 School of Pharmacy and Pharmacology University of Tasmania Hobart TAS Australia
– name: 5 Discipline of Pharmacy Graduate School of Health University of Technology Sydney Ultimo NSW Australia
– name: 6 Centre for Inflammation Centenary Institute Faculty of Science School of Life Sciences University of Technology Sydney NSW Australia
– name: 7 Institute for Molecular Bioscience University of Queensland St Lucia QLD Australia
– name: 1 Department of Molecular and Translational Science Monash University Clayton VIC Australia
– name: 2 Centre for Cancer Research Hudson Institute of Medical Research Clayton VIC Australia
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  organization: University of Technology
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Copyright 2021 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
2021. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: 2021 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
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Issue 2
Keywords NLRP3
inflammatory disorder
inflammasome
endoplasmic reticulum stress
Language English
License Attribution-NonCommercial-NoDerivs
2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
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wiley_primary_10_1002_cti2_1247_CTI21247
PublicationCentury 2000
PublicationDate 2021
PublicationDateYYYYMMDD 2021-01-01
PublicationDate_xml – year: 2021
  text: 2021
PublicationDecade 2020
PublicationPlace Australia
PublicationPlace_xml – name: Australia
– name: Milton, Queensland
– name: Hoboken
PublicationTitle Clinical & translational immunology
PublicationTitleAlternate Clin Transl Immunology
PublicationYear 2021
Publisher John Wiley & Sons, Inc
John Wiley and Sons Inc
Wiley
Publisher_xml – name: John Wiley & Sons, Inc
– name: John Wiley and Sons Inc
– name: Wiley
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Snippet Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and...
Abstract Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against...
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SubjectTerms Allergens
Alzheimer's disease
Arteriosclerosis
Asthma
Atherosclerosis
Binding sites
Biosynthesis
Chronic obstructive pulmonary disease
Diabetes
Endoplasmic reticulum
endoplasmic reticulum stress
Homeostasis
Immune system
Infections
inflammasome
Inflammasomes
Inflammation
Inflammatory bowel disease
Inflammatory bowel diseases
Inflammatory diseases
inflammatory disorder
Intestine
Kinases
Lung diseases
Metabolism
NLRP3
Obstructive lung disease
Pathogenesis
Pathogens
Physiology
Protein folding
Protein synthesis
Quality control
Review
Rheumatoid arthritis
Sarcoidosis
Therapeutic targets
Transcription factors
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Title The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome: a potential therapeutic target for inflammatory disorders
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